title: Electroacupuncture improves gut barrier dysfunction in prolonged hemorrhagic shock rats through vagus anti-inflammatory mechanism.
abstract: OBJECTIVE
  To investigate whether electroacupuncture (EA) at Zusanli (ST36) prevents intestinal barrier and remote organ dysfunction following prolonged hemorrhagic shock through a vagus anti-inflammatory mechanism.
  
  
  METHODS
  Sprague-Dawley rats were subjected to about 45% of total blood volume loss followed by delayed fluid replacement (DFR) with Ringer lactate 3h after hemorrhage. In a first study, rats were randomly divided into six groups: (1) EAN: EA at non-channel acupoints followed by DFR; (2) EA: EA at ST36 after hemorrhage followed by DFR; (3) VGX/EA: vagotomy (VGX) before EA at ST36 and DFR; (4) VGX/EAN: VGX before EAN and DFR; (5) α-bungarotoxin (α-BGT)/EA: intraperitoneal injection of α-BGT before hemorrhage, followed by EA at ST36 and DFR; and (6) α-BGT/EAN group: α-BGT injection before hemorrhage followed by EAN and DFR. Survival and mean arterial pressure (MAP) were monitored over the next 12 h. In a second study, with the same grouping and treatment, cytokine levels in plasma and intestine, organ parameters, gut injury score, gut permeability to 4 kDa FITC-dextran, and expression and distribution of tight junction protein ZO-1 were evaluated.
  
  
  RESULTS
  MAP was significantly lowered after blood loss; EA at ST36 improved the blood pressure at corresponding time points 3 and 12 h after hemorrhage. EA at ST36 reduced tumor necrosis factor-α and interleukin (IL)-6 levels in both plasma and intestine homogenates after blood loss and DFR, while vagotomy or intraperitoneal injection of α-BGT before EA at ST36 reversed its anti-inflammatory effects, and EA at ST36 did not influence IL-10 levels in plasma and intestine. EA at ST36 alleviated the injury of intestinal villus, the gut injury score being significantly lower than that of EAN group (1.85 ± 0.33 vs 3.78 ± 0.59, P < 0.05). EA at ST36 decreased intestinal permeability to FITC-dextran compared with EAN group (856.95 ng/mL ± 90.65 ng/mL vs 2305.62 ng/mL ± 278.32 ng/mL, P < 0.05). EA at ST36 significantly preserved ZO-1 protein expression and localization at 12 h after hemorrhage. However, EA at non-channel acupoints had no such effect, and abdominal vagotomy and α-BGT treatment could weaken or eliminate the effects of EA at ST36. Besides, EA at ST36 decreased blood aminotransferase, MB isoenzyme of creatine kinase and creatinine vs EAN group at corresponding time points. At the end of 12-h experiment, the survival rate of the EA group was significantly higher than that of the other groups.
  
  
  CONCLUSIONS
  EA at ST36 attenuates the systemic inflammatory response, protects intestinal barrier integrity, improves organ function and survival rate after hemorrhagic shock via activating the cholinergic anti-inflammatory mechanism.
authors.affiliation: Ming-Hua Du, Hong-Min Luo, Sen Hu, Yi Lv, Zhi-Long Lin, Li Ma, Research Laboratory of Shock and Multiple Organ Dysfunction, Burns Institute, First Hospital Affiliated to the PLA General Hospital, Beijing 100048, China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Du
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Luo
authors.forename: Sen
authors.initials: S
authors.lastname: Hu
authors.forename: Yi
authors.initials: Y
authors.lastname: Lv
authors.forename: Zhi-Long
authors.initials: ZL
authors.lastname: Lin
authors.forename: Li
authors.initials: L
authors.lastname: Ma
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D002038:Bungarotoxins / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D015671:Electroacupuncture; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018836:Inflammation Mediators / Q000097:blood; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000294:innervation* / Q000473:pathology; D008297:Male; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D014628:Vagotomy; D014630:Vagus Nerve / Q000503:physiopathology* / Q000601:surgery; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D002038:Bungarotoxins; D016207:Cytokines; D018836:Inflammation Mediators; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein
keywords: Electro-acupuncture; Hemorrhagic shock; Intestinal permeability; Tight junction; Zusanli